Cannabis has long been used for medicinal purposes and as a recreational drug. The medicinal application is essentially anti-emetic, i.e. that the active components of cannabis, i.e. cannabinoids, are effective as a drug against nausea and vomiting which are commonly side-effects of opioid analgesics, anaesthetics, highly active anti-retroviral therapy (HAART for HIV-AIDS) and chemotherapy for cancer. Cannabis has also been used for a long period of time as a drug for relieving (chronic neurogenic/neuropathic) pain that is caused by several disorders and surgical operations. Other medical indications include depression, migraine, multiple sclerosis, fibromyalgia, syndromes like Parkinson and Gilles de la Tourette and its use as analgesic, spasmolytic, appetite stimulating, palliative and anti-convulsant medication.
The main constituent of cannabis is delta-9-tetrahydrocannabinol (THC) or dronabinol. Its IUPAC nomenclature is (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol). THC binds to the cannabinoid receptor CB1 (agonist) which is located in brain tissue. Other active components of cannabis include cannabidiol (CBD; 2-((1S,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)-5-pentylbenzene-1,3-diol) and cannabichromene (CBC). CBD is not binding to the CB1 or the CB2 receptor whereas CBC is believed to have an anti-inflammatory action and would contribute to the pain relieving effect of cannabis.
Cannabis is usually inhaled by the patient (cannabis is often mixed with tobacco for smoking purposes). Smoking has a rapid onset (minutes) and the dosage can be easily controlled by the patient. However, smoking is not always convenient, since it is reported to have an adverse affect on the respiratory system and many patients just dislike smoking. Additionally, smoking of cannabis includes burning of the herb which may lead to the formation of harmful side-products like noxious carbon monoxide. Furthermore, the harmful effects of nicotine and tar are well known. Although effective, smoking cannabis has many disadvantages.
Another method frequently employed is vaporisation wherein the herb is heated to about 180° C. rather than burned so that harmful side-products are hardly formed. Additionally, the vapour may be cooled or further purified if desired before inhalation. Furthermore, the dosage is easily controlled by the patient since inhalation provides for a rapid onset and a fast delivery into the bloodstream. However, the use of a vaporiser is also not always convenient since it requires a place or spot where the patient can set up and use his or her vaporiser to undergo treatment. In this respect it is also time-consuming.
Oral compositions comprising synthetic THC, e.g. gelatine capsules and tablets, are also known in the art. Marinol® (active component is dronabinol or (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol) is a soft gelatine capsule à 2.5 mg comprising synthetic THC. A disadvantage of this product is the high price and that it takes about an hour to take full effect and the frequent dosage problems encountered by patients. The bio-availability after oral intake is only approximately 15%. Namisol® (active component is dronabinol) is a sublingual tablet à 1.4 mg THC (ultra pure extract from cannabis sativa), which is claimed to have a rapid uptake through the sublingual mucosa. The problem is that the tablet has to be kept under the tongue for the time it takes to dissolve in the saliva.
Cesamet® (active component is nabilone) is a capsule comprising the synthetic cannabinoid nabilone (racemic (6aR,10aR)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-7,8,10,10a-tetrahydro-6H-benzo[c]chromen-9(6aH)-one). It is said to have fewer undesired side effects than THC.
Sativex® comprises THC and CBD and is commercially available as a buccal mouth spray for multiple sclerosis and for the alleviation of pain. Each spray of Sativex® delivers a fixed dose of 2.7 mg THC and 2.5 mg CBD. It is reported to cause irritation of the oral mucosa (20-25% of the patients) and to have a bad taste because of the high ethanol content.
However, gelatine capsules comprising THC or similar components appear to be less effective than smoking cannabis or vaporising cannabis and inhaling the vapour formed. Moreover, patients suffering from severe nausea due to chemotherapy complained that these oral formulations were difficult to swallow.
GB 2377633 of GW Pharmaceuticals, incorporated by reference, discloses pharmaceutical compositions comprising cannabinoids having specific ratios of cannabidiol (CBD) to tetrahydrocannabinol (THC). The compositions are clinically useful in the treatment or management of specific diseases or medical conditions.
GB 2381194 of GW Pharmaceuticals, incorporated by reference, discloses pharmaceutical formulations for use in the administration of medicaments, in particular lipophilic medicaments, via mucosal surfaces. Example 9 discloses a formulation for buccal use and sublingual tablets.
GB 2414933 of GW Pharma Ltd., incorporated by reference, discloses the use of a combination of cannabinoids for the treatment of pain, inflammation and/or disease modification in arthritis. The cannabinoids are selected from CBD or cannabidivarin (CBDV) and THC or tetrahydrocannabinovarin (THCV) and are in a predefined ratio by weight of less than or equal to 19:1 of CBD or CBDV to THC or THCV.
GB 2432312 of GW Pharma Ltd., incorporated by reference, discloses the use of a combination of cannabinoids in the treatment of neuropathic pain, in particular peripheral neuropathic pain. A combination of CBD and THC may be used, wherein the ratio of CBD:THC by weight is between 10:1 and 1:10.
There is still a need in the art for a composition comprising a cannabinoid that can be used by a mammal, preferably a human, suffering from pain for the treatment or alleviation of said pain, wherein said composition can be used in a mammal friendly, preferably man-friendly, and socially accepted manner including situations and locations where smoking is legally not allowed or is not convenient or is hampering or irritating other mammals, preferably humans, such as in restaurants, train stations, café's and the like. There is further a need in the art for a composition comprising a cannabinoid or a derivative thereof that can be used as a unit dosage form, in particular a unit dosage form that is easily and safely packed in a suitable carrier, e.g. a blister package so that it can be easily carried by the consumer. There is also a need in the art for compositions comprising a cannabinoid or a derivative thereof that allows for controlled release of the cannabinoid or the derivative thereof. Additionally, there is a need in the art for better dissolving of lipophilic cannabinoids and improving or masking the unpleasant taste of these lipophilic cannabinoids.